Steroids: Salt - Sugar - Sex.

Steroid hormones are essential for life. These hormones are produced by the gonades (testes and ovaries), the adrenal cortex, the placenta and the brain. Thus their function is important for sexual development and fertility (sex steroids) as well as water, salt and glucose balance of the body in stress (mineralocorticoids and glucocorticoids). Mutations in involved genes therefore cause disorders of sexual development (DSD) and congenital adrenal hyperplasia. Most genes involved in steroid biosynthesis are long known and human mutations provide an excellent model for studying their exact function in human biology. Progress has been made in genotype-phenotype and structure-function prediction by combining clinical, experimental and bioinformatic data. Recently, the importance of cofactors and modulators has been illustrated. P450 oxidoreductase (POR) is an obligate electron donor to many P450 enzymes. POR deficiency mimicks combined 21- and 17-hydroxylase deficiency and manifests with adrenal insufficiency and disordered sex development but may also affect bone development and drug metabolism and more. Steroidogenic factor 1 (SF-1) is a transcription factor regulating most genes involved in steroid biosynthesis and sex development. Heterozygote SF-1 mutations cause a wide range of DSD in 46,XY individuals and premature ovarian failure in 46,XX.

Because SF-1 mutations cause this broad spectrum of disease which we still do not fully understand, co-regulators may exist and are currently searched for.

Investigador de contacte:

Dra. Laura Audí

laura.audi@vhir.org